Rapid hepatitis C virus replication machinery removal after antiviral treatment with DAA monitored by multimodal...

Hepatitis C virus (HCV) replication causes a profound remodeling of the host endomembrane system. The availability of direct-acting antiviral (DAA) drugs provides an opportunity to define the ultrastructural events that follow viral replication blockade using confocal immunofluorescence, transmission electron microscopy (TEM) as well as correlative cryogenic light-soft X-ray tomography (CLSXT). Study of DAA-treated HCV replicons using CLSXT indicates that HCV-induced membranous alterations are no longer visible after 24 h of treatment and that a component of the replicase is located in pleomorphic, high-absorption contrast acidic organelles. TEM studies confirmed the rapid elimination of the viral machinery, and the concurrent appearance of large endo-lysosomes in DAA-treated cells. These and results by others suggest that HCV replication compartment may constantly be recycled by the endo-lysosomal system and that this equilibrium is unbalanced by DAA treatment, resulting in a transient activation of the endo-lysosomal system to achieve rapid viral machinery removal.